Table 2 Key changes from the 2018 to the current consensus recommendations on medical therapy outcomes

SRL treatment outcomes

Not specifically detailed for specific treatment and not included in the table of 2018 recommendations

GH and IGF1 levels: IGF1 is the preferred marker to monitor SRL therapy; IGF1 should be measured after the first three injections, and further IGF1 measurements depend on the degree and rate of IGF1 reduction

Effect on adenoma shrinkage: biochemical results might be useful to guide follow-up imaging frequency; in SRL-responsive acromegaly, adenoma growth and progression are rare, and routine pituitary MRI surveillance is not recommended; imaging should be triggered particularly by visual or eye movement symptoms or withdrawal of treatment and initiation of radiation therapy

Clinical responses: increased focus on patient-reported outcome measures required; clinical parameters should be standardized, and accepted criteria for defining improvements in signs and symptoms are needed; symptoms and clinical evaluation, related to both acromegaly and medications, and monitoring comorbidities and potential adverse events; clinicians should be aware of discrepancies between clinical and biochemical outcomes; however, symptom burden should still be considered when deciding therapeutic approaches and the use of clinical tools and questionnaire remains crucial

Adverse effects: routine periodic abdominal ultrasound monitoring is not supported; routine monitoring of glucose levels with all SRLs and especially for pasireotide; caution when administered with other medications interfering with QT intervals

Pegvisomant treatment outcomes

Not specifically detailed for specific treatment and not included in the table of 2018 recommendations

IGF1 levels: IGF1 is the biomarker for pegvisomant therapy monitoring; maximal IGF1 lowering effect is achieved within 4–6 weeks with dose titration

Adenoma mass: yearly pituitary MRI monitoring is no longer considered necessary; after SRL withdrawal imaging might be performed within 6–12 months after starting pegvisomant

Clinical features: symptoms, QoL and comorbidities often improve and should be monitored; disease control is accompanied by improved sleep apnoea syndrome, hypertension, arthralgia and glucose homeostasis

Adverse effects: lipodystrophies can be minimized by rotation of injection sites; liver function tested before starting and monitored during dose titration; discontinue when transaminase levels exceed five times the ULN

Combination therapy

Not specifically detailed for specific treatment and not included in the table of 2018 recommendations

Cabergoline and pegvisomant: no firm evidence supporting this combination; might be considered, with potential to save costs, in patients with acromegaly resistant to SRLs, not controlled by pegvisomant alone and responsive to cabergoline

SRLs and pegvisomant: useful and safe therapeutic approach in patients with acromegaly partially responsive to SRLs alone, or those with adenoma size increase during pegvisomant monotherapy or diabetes mellitus; higher risk of increased levels of liver enzymes than pegvisomant alone

Pasireotide and pegvisomant: to consider in patients with acromegaly who do not respond to first-line and second-line medical treatment; high costs and no long-term efficacy information

Treatment outcome goals (2018)

Biochemical outcomes: measuring both GH and IGF1 levels; normalizing levels of IGF1 is a key goal; wait at least 12 weeks after surgery to assess IGF1 levels; using the same assay with accepted performance standards when monitoring IGF1 levels over time

Specifically detailed for specific treatments in the current consensus recommendations (see the previous rows in this table)

Adenoma volume: reducing adenoma size and preventing persistent growth are relevant goals for patients with macroadenomas; reduction in diameter, rather than adenoma volume, is reproducible and sufficient to assess meaningful mass change

Clinical symptoms: assessing and managing hypertension and cardiac hypertrophy, diabetes mellitus and glucose intolerance, sleep apnoea and osteopathy is recommended; clinician-reported outcome instruments can be used to monitor indicators of disease activity

Second-line medical therapy if SRL is not successful in normalizing IGF1

Partial response: increase SRL dose and/or increase frequency of lanreotide dosing; add cabergoline to SRL if IGF1 is moderately elevated

Increasing SRL dose and/or frequency even though off-label use

Minimal or no response and mass concern: switch to pasireotide LAR

Pasireotide if relevant residual adenoma tissue in patients with acromegaly not adequately controlled on SRLs

Minimal or no response and impaired glucose metabolism: switch to pegvisomant

Combination of SRLs with pegvisomant is effective in most patients

Minimal or no response, mass concern and impaired glucose metabolism: add pegvisomant to SRL

Pegvisomant plus cabergoline might be considered when SRLs plus pegvisomant is not feasible due to SRL intolerance

Therapy if biochemical control is not achieved after second-line therapy

Stereotactic radiosurgery or surgical intervention (or reintervention). Temozolomide for unusually aggressive or proven malignant tumours (in close cooperation with a neuro-oncologist)

Limited but promising results of pasireotide with pegvisomant in patients with poorly responsive acromegaly

Combination of pegvisomant with cabergoline if patients resistant to SRLs, not controlled by pegvisomant

Temozolomide and other chemotherapies limited for particularly aggressive or malignant lesions undergoing radiation therapy with neuro-oncology supervision

Use of clinical outcome instruments

Objective tools (SAGIT and ACRODAT) can be used to assess and monitor indicators of disease activity. Patient QoL questionnaires (AcroQoL) are probably of limited value

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